HUMAN OLFACTORY EPITHELIAL CELLS GENERATED IN VITRO EXPRESS DIVERSE NEURONAL CHARACTERISTICS

被引：45

作者：

Borgmann-Winter, K. E. ^{[2
,3
]}

Rawson, N. E. ^{[1
]}

Wang, H. -Y. ^{[4
]}

Wang, H. ^{[5
]}

Macdonald, M. L. ^{[6
]}

Ozdener, M. H. ^{[1
]}

Yee, K. K. ^{[1
]}

Gomez, G. ^{[7
]}

Xu, J. ^{[1
]}

Bryant, B. ^{[1
]}

Adamek, G. ^{[8
]}

Mirza, N. ^{[9
]}

Pribitkin, E. ^{[10
]}

Hahn, C. -G. ^{[2
]}

机构：

[1] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA

[3] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat, Philadelphia, PA 19104 USA

[4] CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY 10075 USA

[5] Fudan Univ, Genet Res Inst, Shanghai 200433, Peoples R China

[6] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA

[7] Univ Scranton, Dept Biol, Scranton, PA 18510 USA

[8] Mol Devices Corp, Downingtown, PA 19335 USA

[9] Univ Penn, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA

[10] Thomas Jefferson Univ, Dept Otorhinolaryngol, Philadelphia, PA 19107 USA

来源：

NEUROSCIENCE | 2009年 / 158卷 / 02期

基金：

美国国家科学基金会;

关键词：

neurogenesis; odorant receptor; NMDA receptor; 5-HT receptor; dopamine receptor; neuronal cell culture; DOPAMINE D2 RECEPTOR; ADULT; RAT; DIFFERENTIATION; CULTURES; NEUROGENESIS; SEROTONIN; CHANNEL; MOUSE;

D O I：

10.1016/j.neuroscience.2008.09.059

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The olfactory epithelium constitutes the sole source of regenerating neural cells that can be obtained from a living human. As such, primary cultures derived from human olfactory epithelial biopsies can be utilized to study neurobiological characteristics of individuals under different conditions and disease states. Here, using such human cultures, we report in vitro generation of cells that exhibit a complex neuronal phenotype, encompassing receptors and signaling pathways pertinent to both olfaction and other aspects of CNS function. Using in situ hybridization, we demonstrate for the first time the native expression of olfactory receptors in cultured cells derived from human olfactory epithelial tissue. We further establish the presence and function of olfactory transduction molecules in these cells using immunocytochemistry, calcium imaging and molecular methods. Western blot analysis revealed the expression of neurotransmitter receptors for dopamine (D2R), 5-HT (5HT2C) and NMDA subtypes 1 and 2A/2B. Stimulation with dopamine or 5-HT enhanced receptor G protein activation in a subtype specific manner, based on 35S-guanosine triphosphate incorporation assay. Functional characteristics of the cultured cells are demonstrated through enhanced tyrosine phosphorylation of NMDAR 2A/2B and recruitment of signaling partners in response to NMDA stimulation. The array of neuronal characteristics observed here establishes that proliferating cells derived from the human olfactory epithelium differentiate in vitro to express functional and molecular attributes of mature olfactory neurons. These cultured neural cells exhibit neurotransmitter pathways important in a number of neuropsychiatric disorders. Their ready availability from living humans thus provides a new tool to link functional and molecular features of neural cells with clinical characteristics of individual living patients. (c) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：642 / 653

页数：12

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